Recent reports indicate that combination chemotherapy may have more activity than single agent DTIC in metastatic melanoma. In particular, the regimen of DTIC, cisplatin, BCNU and tamoxifen, as well as the regimen of interferon-alpha and cisplatin have both shown promising activity. In this trial, we have combined what may be the essential elements of each of these two regimens into an outpatient regimen of cisplatin, interferon-alpha and tamoxifen. Carboplatin has been added to provide higher total doses of platinum. The drugs were administered in a 28 day cycle as follows: carboplatin, 400 mg/m2 IV day 0, cisplatin, 25 mg/m2 IV day 7, 14, 21, tamoxifen, 20 mg po bid, and interferon-alpha 5 million units/m2 TIW. Ten patients are currently evaluable for toxicity and response. Twenty-two cycles of therapy have been administered. The major toxicity was hematologic with six episodes of equal to or greater than grade III neutropenia, six episodes of equal to or greater than grade III thrombocytopenia, and two episodes of grade III anemia. Six patients required treatment delays or dose adjustments of platinum or interferon-alpha for hematologic toxicity. Two patients had greater than or equal to grade II nausea and vomiting. Four patients complained of worsening fatigue with therapy. There have been two short lived partial responses, two mixed responses, and six patients demonstrated progressive disease. It thus appears that this regimen-causes significant toxicity without substantial antitumor activity.